Prado Carla M M, Baracos Vickie E, McCargar Linda J, Mourtzakis Marina, Mulder Karen E, Reiman Tony, Butts Charles A, Scarfe Andrew G, Sawyer Michael B
Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
Clin Cancer Res. 2007 Jun 1;13(11):3264-8. doi: 10.1158/1078-0432.CCR-06-3067.
Evidence suggests that lean body mass (LBM) may be useful to normalize doses of chemotherapy. Data from a prospective study were used to determine if the highest doses of 5-fluorouracil (5-FU) per kilogram LBM would be associated with dose-limiting toxicity in stage II/III colon cancer patients treated with 5-FU and leucovorin.
Toxicity after cycle 1 was graded according to National Cancer Institute Common Toxicity Criteria, version 2.0. Muscle tissue was measured by computerized tomography. An extrapolation to the LBM compartment of the whole body was employed.
Mean values of 5-FU/LBM of the entire population were different in terms of presence or absence of toxicity (P = 0.036). A cut point of 20 mg 5-FU/kg LBM seemed to be a threshold for developing toxicity (P = 0.005). This observation was pertinent to women (odds ratio, 16.73; P = 0.021). Women in this study had a relatively low proportion of LBM relative to their body surface area.
Our study shows that low LBM is a significant predictor of toxicity in female patients administered 5-FU using the convention of dosing per unit of body surface area. We conclude that variation in toxicity between females and males may be partially explained by this feature of body composition.
有证据表明，瘦体重（LBM）可能有助于使化疗剂量标准化。一项前瞻性研究的数据被用于确定在接受5-氟尿嘧啶（5-FU）和亚叶酸治疗的II/III期结肠癌患者中，每千克瘦体重使用最高剂量的5-FU是否会与剂量限制性毒性相关。
根据美国国立癌症研究所通用毒性标准第2.0版对第1周期后的毒性进行分级。通过计算机断层扫描测量肌肉组织。采用对全身瘦体重部分的外推法。
整个人群的5-FU/瘦体重平均值在有无毒性方面存在差异（P = 0.036）。20 mg 5-FU/千克瘦体重的切点似乎是发生毒性的阈值（P = 0.005）。这一观察结果与女性相关（优势比，16.73；P = 0.021）。本研究中的女性相对于其体表面积的瘦体重比例相对较低。
我们的研究表明，在按照每单位体表面积给药的惯例给予5-FU的女性患者中，低瘦体重是毒性的重要预测指标。我们得出结论，女性和男性之间毒性的差异可能部分由这种身体组成特征来解释。
